The overall objective is a general methodology for using knowledge of one or more active ligands to select from among the vast realm of all synthetically accessible structures the most promising compounds for some particular therapeutic objective, to be used by medicinal chemists directly. A novel topomeric descriptor has been providing very rapid and effective shape similarity searching of combinatorial "virtual libraries". However that technology would not succeed in "discovering" structures whose syntheses involve many steps, including most drugs on the market. Therefore, during Phase I, technologies were developed for representing and topomerically searching products of multistep synthesis, by repeatedly applying reactions to reagents and generating topomers for each of the resulting synthons. Validation experiments suggest that roughly 10E20 "drug-like" structures will now be searchable overnight, including about half of those appearing in the medicinal chemistry literature. As the critical question then becomes "is the proposed synthesis practical", individual synthetic chemists become the key decision makers. Therefore Phase II activities emphasize adding value for such users of the system. Its numerous projects have two general objectives, building a satisfactory user interface including dynamic reaction data management, and broadening the new techniques for representing synthesis outcomes in topomerically searchable forms, thereby covering more chemistry better.